Air pollution is ubiquitous but very little is known about adverse effects it may have on the developing brain during fetal life. Recently it has been hypothesized that air pollution acts on biologic pathways contributing to autism spectrum disorder (ASD), one of the most severe neurodevelopmental disorders in children with large increases in incidence over the past two decades in the U.S.. The small number of studies to date that examined air pollution and autism have employed various crude exposure measures, or have been small in size, or have limited interpretability since they could only adjust for a few confounding factors. To fill this gap in knowledge we will utilize Danish nationwide population-based registers and sophisticated individual-level air pollution exposure measures to assess whether early life exposure to traffic-related and particulate air pollution during critical period of fetal development are associated with ASD risk. Denmark has a long-standing tradition of maintaining one of the world's largest health science information data banks and has provided tax- supported health care and prescription medication coverage for all residents for many decades; data not yet available in the U.S.. Through existing collaborations with Denmark (R01ES013717, R03ES021643), we have access to and gained a solid understanding of these unique resources. There are ~8,087 Danish children with ASD born since 1989 and we aim to match them on birth year and sex to a comparison population of control children at a ratio of 1:4 based. We will utilize a sophisticated and validated GIS-based dispersion model, AirGIS, to assess prenatal and early life exposures to traffic-related and particulate air pollution. Our collaborator, Dr. Raaschou-Nielsen, employed the traffic pollutant model successfully to assess cancer risk.6,7 Exposure is modeled in AirGIS based on nitrogen dioxides (NO2)/nitrogen oxides (NOx) serving as indicators for pollution mixtures from traffic and a nationwide emissions based model that provided estimates for PM2.5 and PM10 at high spatial and temporal resolution; both models allow us to create address level individual exposure measures. The specific aims of our study are to: (1) establish the largest nationwide population based study of childhood autism and air pollution worldwide; and (2) test the hypothesis that exposure to air pollution during critical periods of fetal development are associated with autism. In addition, we will use the Danish National Birth Cohort (DNBC) which enrolled pregnant women and collected extensive prospective risk factor data during pregnancy and early life for ~100,000 children among whom 720 are already diagnosed with ASD to examine potential confounding bias for a large number of risk factors assessed in pregnancy. Our focus on individual level estimates of traffic-related air pollution will advance existing knowledge about air pollution related toxins an their detrimental impact on neurodevelopment. Furthermore, the proposed study will provide policy makers with evidence to support air pollution regulation, transportation and goods movement policies and may have implications for the preservation of neurological function in susceptible children.